PROJECT DESCRIPTION Co-factors linked to high-risk (hr) HPV persistence versus transience are not well-defined. Deficiencies in nutrients such as vitamin D can increase the risk of carcinogenesis via DNA damage, immune incompetence, and genetic alterations. While a recent study reported that vitamin D deficiency was associated with an increased likelihood of prevalent hrHPV infection, to our knowledge, no study has explored associations between vitamin D levels and hrHPV persistence or reactivation. From 2011-2012, we recruited 409 healthy mid-adult women to participate in a 6-month longitudinal study of hrHPV infections. Each month, women self- collected vaginal samples for PCR-based genotype-specific hrHPV DNA testing and completed health and sexual behavior questionnaires. In addition, sera were collected for hrHPV serology testing and future biomarker testing. We propose to make efficient use of stored sera, monthly hrHPV genotyping results, and hrHPV serology results to evaluate vitamin D levels in relation to presence, persistence, and reactivation of hrHPV infection. To explore different potential mechanisms of vitamin D involvement, sera will be tested for several different biomarkers: 25-hydroxyvitamin D (25(OH)D) and several alternative measures that may better characterize vitamin D sufficiency, including 1,25-dihydroxyvitamin D (1,25(OH)2D), free vitamin D, and bioavailable vitamin D. Our aims are to: 1) Evaluate cross-sectional associations between serum vitamin D levels and prevalent hrHPV infection; 2) Evaluate associations between serum vitamin D levels and persistent vs. transient type-specific hrHPV infection; and 3) In women with evidence of prior hrHPV infection at baseline (positive serology / negative DNA), evaluate the association between serum vitamin D levels and subsequent reactivation of the same hrHPV type. We hypothesize that higher serum vitamin D levels will be inversely associated with prevalent, persistent, and reactivated hrHPV infection. Information gleaned will help us to understand whether serum vitamin D levels impact the hrHPV natural history in mid-adult women. Ultimately, these pilot data will be crucial in developing future longitudinal studies designed to evaluate whether achievement or maintenance of sufficient serum vitamin D levels can positively alter the natural history of hrHPV infections.